SUPPLEMENT ARTICLE

The Safety Record of Fusidic Acid in Non-US

Markets: A Focus on Skin Infections
Carl N. Kraus1 and Barry W. Burnstead2
1Infectious

Diseases, Nanotherapeutics, Inc, Alachua, Florida; and 2Clinical Data Interchange Standards Consortium, Austin, Texas

There is great concern regarding the increasing problem

of drug resistance among salient organisms, termed
ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter
baumannii, Pseudomonas aeruginosa, and Enerobacter
spp.), that are responsible for the majority of hospitalacquired infections [13]. Frequently cited as one of the
factors fueling alarm is the shrinking antimicrobial armamentarium available to clinicians for illnesses caused
by these pathogens. There are, however, drugs available
on the global market outside the United States with
demonstrated activity against some of these organisms,
as well as efficacy in treatment of consequent infections.
For example, there are widely utilized drugs effective
against staphylococcal infections, including methicillinresistant S. aureus (MRSA), that have not yet entered the

Correspondence: Carl N. Kraus, MD, Nanotherapeutics Inc, 13859 Progress Blvd,

Suite 300, Alachua, FL 32615 (ckraus@nanotherapeutics.com).
Clinical Infectious Diseases 2011;52(S7):S527S537
The Author 2011. Published by Oxford University Press on behalf of the
Infectious Diseases Society of America. All rights reserved. For Permissions,
please e-mail: journals.permissions@oup.com.
1058-4838/2011/52S7-0009$14.00
DOI: 10.1093/cid/cir168

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Fusidic acid has been in clinical use outside the United States (US) since 1962 for skin infections, including
methicillin-resistant Staphylococcus aureus (MRSA). Non-US labeling reflects safety concerns related to
gastrointestinal, allergic, hematologic, and neurologic adverse events. We sought to survey available safety data
on fusidic acid through the review of published global literature between 1962 and 2007 that contained data on
oral fusidic acid safety and a centralized database (VigiBase) of spontaneous safety reports. Overall, the data
were concordant with current product labeling, and no serious adverse events, such as death, hospitalization, or
hepatotoxicity, were convincingly linked to fusidic acid monotherapy in skin infection patients. Other
indications for fusidic acid use were also common, including osteomyelitis with similar reporting of labeled
safety characteristics. Study quality was highly varied with limited structure to safety data collection
methodology. Significant concerns for recall bias are present, yet these data remain informative in providing
signals that require attention in the design and conduct of adequate and well-controlled clinical studies of
fusidic acid for potential registration in the United States.

US pharmaceutical marketplace. Efforts focused on

seeking marketing approval for such drugs would (1)
result in a better understanding of safe use prior to
market entry and (2) possibly lessen the regulatory demand for larger safety databases for registrational review
when compared with bringing a new molecular entity
(NME) to market. It would also have the additional
benefit, over standard applications, of an ethnically diverse safety database to bolster a New Drug Application
(NDA) to the US Food and Drug Administration
(FDA).
One such drug is fusidic acid (FA), which has been in
clinical use for the treatment of staphylococcal infections outside the United States since 1962. FA is
marketed in at least 23 countries with an estimated 21.3
million prescriptions annually (2006), of which 1.3
million were for oral use (IMS dataon file). This
widespread use has resulted in a comprehensive collection of spontaneous adverse event reports related to FA
as well as citations regarding clinical use since FA entered the pharmaceutical market 48 years ago. These
safety data are accessible and provide insight into events
that might be expected should FA become available for
use in the United States. Precedents for the pooling of
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such data exist and have supported other drugs as they enter the
US market, such as the tinidazole NDA by Presutti Labs (Nos.
21-618, 21-681, and 21-682 for trichomoniasis, giardiasis, and
amebiasis, respectively) on 14 May 2005 and the quinine sulfate
NDA (No. 21-799 for the treatment of uncomplicated
Plasmodium falciparum infection) by Mutual Pharmaceutical
Co on 8 August 2005. Clinical safety data were systematically
extracted from the published literature according to a predefined review process. Each publication needed to meet clear
inclusion criteria to be included in the authors safety database
(Table 1).
FUSIDIC ACID SAFETY CONSIDERATIONS IN
FOREIGN LABELS

1. Gastrointestinal: flatulence, vomiting, nausea, hepatic

transaminase elevation, diarrhea, anorexia, abdominal pain,
jaundice, dyspepsia

The frequency of most events was low or occurred at a low

enough severity that inclusion in labeling was sufficient for
foreign regulatory authorities to ensure safe and effective use of
FA. Various precautions regarding concomitant drug administration and use in patients with impaired liver function are included in the labeling to limit potential hepatic AEs.
FUSIDIC ACID SAFETY DATA POOLED FROM
THE PUBLISHED LITERATURE
The published literature was reviewed for evidence of use of
oral FA alone or use of oral FA after intravenous use of FA in
human subjects so that clinical safety data could be pooled. The
primary objective was to determine if the available data adequately reflected foreign product labeling and to describe AEs
associated with FA use according to character, frequency, and
severity.
In order to identify relevant citations that included clinical
safety data, a literature search was conducted using a medical
subject heading (MeSH) query for fusidic acid in the Medline
database (19542007) and the Wolters Kluwer Adis Journals
database, resulting in the identification of 1252 unique citations
as of 21 April 2007 that were subsequently screened for any
reference to the clinical use of FA. The citation abstracts were
reviewed to assess clinical relevancy, defined by human

Table 1. Fusidic Acid Literature Search Methodology

Step

Search details

Citations, no.

Total

1
2

MeSH FA 1 Therapeutic Use 1 Limit to Human

(FA/administration and dosage[MeSH] OR FA/adverse effects[MeSH] OR FA/metabolism[MeSH] OR FA/pharmacokinetics[MeSH] OR FA/therapeutic use[MeSH] OR FA/
toxicity[MeSH]) Limits: Humans

478
17

478
495

MeSH FA 1 Adverse Events - Limit to Human

80

575

200

775

553

222

44

266

270

PubMed searches

Additional citations identified

4
Combining search strategies
First review
5

Reviewed the list identifying those citations likely to contain clinical safety information based
upon the article title or, when readily available, the abstract. Eliminated duplicates and publications that clearly had no clinical content.

ADIS searches
6

MeSH FA 1 Therapeutic Use 1 Limit to Human

MeSH FA and Adverse Events

British Medical Journal and associated journalssearch

8

MeSH FA in title 1 FA in text. Identified new citations not in the list so far that include
adverse event information on FA.
NOTE.

S528

FA, fusidic acid; MeSH, medical subject headings.

CID 2011:52 (Suppl 7)

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As in previously reviewed NDAs that incorporate foreign data

[4], there is value in assessing foreign labeling to characterize
safety experience and in identifying likely safety concerns for the
US population should marketing approval be sought and
granted. New Zealand, Canada, the United Kingdom, and Ireland have approved FA for use and have readily available
product labels [5, 6]. The most common dosing schedule in
these labels is 500 mg orally, taken 3 times daily. The 2 most
frequent approved indications in these labels are skin infections
and osteomyelitis. The most common organ systems for which
safety data are cited in the labeling are gastrointestinal, neurologic, allergic, and hematologic. Frequent adverse events (AEs)
described for these systems are:

2. Allergic: rash, pruritis, anaphylaxis, angioneurotic edema,

urticaria, edema
3. Hematologic: leukopenia, anemia, neutropenia, thrombocytopenia, pancytopenia, granulocytopenia, agranulocytosis
4. Neurologic/psychiatric: headache, blurred vision, dizziness,
lethargy, psychic disturbance

Table 2. Fusidic Acid Treatment Indications: Surveyed Literature

(19622007)

Citations, No.

FA dosed
subjects

FA dosed
subjectsa

Skin infection

20

17,192

2520

Osteomyelitis

19

429

429

Other infectious diseases

17

579

579

Autoimmune

15

163

163

Pharmacokinetics

148

148

Pulmonary

438

438

Bacteremia/sepsis
Prosthetic-related

5
5

6
66

6
66

Endocarditis

Cancer

16

16

102

19,045

4373

Indication

Total
a

Without inclusion of Goncalves and Thorn, 1991.

listed were uncharacterized and there were 780 unaccounted

patients in the study, making it difficult to draw any conclusions
regarding safety. Therefore, this study was not included in the
aggregated data set, though independent observations from this
citation alone could complement other findings.
The duration of dosing was assessed by determining the patient exposure to FA and daily consumption. This information
could be determined in 70 of the citations referenced. This
subset of studies contained subjects exposed to FA from 1 day to
240 days with the daily dose ranging from .25 g to 3.75 g. This
considerable variability, combined with the absence of explicit
assignment of the adverse events to the specific patients drug
exposure, was of concern. It was concluded that averaging both
daily drug consumption and duration of exposure introduced
too many assumptions, such that the validity of AE profiling
against exposure time would be in doubt.
Of the 4373 subjects included in the articles reviewed (excluding Goncalves and Thorn [22]), 3287 (75%) had dosing and
scheduling information available; the majority of these subjects
(n 5 2058, 62.6%) received a dose of 500 mg per day or higher.
The other most frequent dosing schedule (n 5 969, 29.5%) was
250 mg twice daily, concordant with the reviewed product labels. The mean daily dose used for treatment of skin infections
ranged from 500 mg to 1500 mg and a large proportion of
patients received 500 mg, 2 or 3 times daily. The mean daily dose
used for treatment of osteomyelitis ranged from 1500 mg to
3000 mg. Fewer data were available for osteomyelitis and there
were no controlled trial data (no osteomyelitis citations had
a comparator arm). Treatment durations were likewise disparate; skin-infection-treated subjects were rarely treated for .10
days (2.4%) and osteomyelitis-treated subjects were rarely
treated for ,10 days (7.9%).
There was marked variability in the methodologies used to
collect safety data in the medical literature surveyed (Table 3).
The majority of the citations (n 5 74) did not address how such
data were collected. As described elsewhere, the manner in
which safety data are collected can impact the overall safety
profile of a drug; spontaneous reporting of AEs is less frequent
than patient reporting [4]. Both methods have disparate sources
of bias (eg, recall bias or reporting bias) with consequent variation in the perceived safety profile of a drug. The majority of
studies of patients treated for skin infections (n 5 20) with oral
FA were uncontrolled observations (n 5 14, 70%), and information regarding how the safety data were collected was not
included. When information was provided (exclusive of the
Goncalves and Thorn citation [22]), the methods were either
not detailed (n 5 12, 60%) or it was specified that data were
collected using specific questionnaires (n 5 7, 35%).
Safety concerns reflecting the character, seriousness, and frequency of adverse events are summarized. Of greatest concern are
the 61 deaths (independent of treatment indication) identified in
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experience, FA exposure, and the availability of data regarding

exposure and safety (Table 1). Qualifying abstracts underwent
full citation review with predetermined exclusions of articles
that included routes of FA administration other than oral, nonEnglish language articles, articles that summarized data from
other articles, and critique articles; 102 articles met the inclusion
criteria and were reviewed (see the Appendix). Prespecified data
extraction criteria were recorded as a line entry in the database
for each article. Some articles addressed different patient groups
and warranted separate line entries. Typically, distinctions were
drawn for the following critera: (1) oral administration where
some patients initially received FA intravenously followed by
oral administration; (2) variable treatment indications; and (3)
variable dosing regimens.
A medical reviewer (board certified in Infectious Diseases)
conducted an independent audit of 10 randomly selected articles
midway through the review process to assess data extraction
quality and clinical relevance. Any relevant findings in this audit
resulted in rereview of the articles and modification of the data
extraction strategy for the remaining articles.
A total of 102 articles published from 1962 to 2007 were
reviewed, resulting in inclusion of 19,045 subjects who had been
exposed to oral FA for a variety of indications (Table 2). The
majority of these studies (n 5 80) were open label (78%). There
were 13 blinded (single or double) studies [719] and 21 randomized trials, 12 of which were controlled, 5 with placebos [10,
16, 17, 20, 21]. One study, by Goncalves and Thorn [22], accounted for the majority (n 5 14,672) of exposures. This uncontrolled, nonrandomized, postmarketing, observational study
assessed the safety and efficacy of oral FA (with and without
concomitant topical FA use) in a general practice setting. The
majority of patients experienced no AEs or reported only minor
(nonserious) events, without description of the frequency, severity, or character of these events. The severe events (n 5 153)

with oral FA, independent of study design. The majority of those

events were classified as gastrointestinal (58%), constitutional
(6.1%), neurologic (3.3%), allergic (4.6%), and other (27%),
with most of the events occurring with the common treatment
regimen of 610 days duration (Table 4). The most common
treatment duration that resulted in an AE was 610 days (80% of
events) and there are no data on the duration associated with 71
(12%) of these events.
There were 429 FA-treated subjects in 19 unique articles on
osteomyelitis, but none contained comparator arm information.
These studies were further confounded by the use of preceding
intravenous FA (31% of subjects). The AEs for subjects receiving
oral FA for osteomyelitis were similar in character to skin infection subjects, with the majority of events classified as gastrointestinal (30%), hepatobiliary (33%), or hematologic
(7.4%). There were 9 hepatobiliary events in this group, yet none
was persuasively linked to oral FA exposure. The subject reported by Biswas et al [31] was receiving numerous concomitant
medications, including hepatotoxic agents. The subjects reported
by Ernst [35] were treated with high-dose FA (mean daily dose of
3 g) and the reference provided insufficient detail to assess the
4 subjects noted to have elevated hepatic enzyme levels.
NON-US SPONTANEOUS SAFETY REPORTS
Because FA has been in clinical use since 1962 in non-US
markets, regulatory authorities around the globe have established their own spontaneous reporting databases for the purpose of capturing postmarketing safety reports in a systematic,
standardized fashion. The majority of these data sources have
restricted access controlled by each local regulatory agency and
could not be accessed. In the UK, however, the Medicines and
Healthcare Products Regulatory Agency provides redacted safety
reports in predefined formats. The report obtained for FA was
wholly inadequate for the purpose of our safety review. In
contrast, the international safety database VigiBase proved to be
of significantly greater value.
Table 4. Adverse Events in Skin Infection Patients Treated With
Oral Fusidic Acid in the Surveyed Literature (19622007)

Table 3. Methodologies for Collecting Safety Data in the

Surveyed Literature
Study design

Organ system

15

610

1120

2160

Not provided

Total

Gastrointestinal

17

275

49

350

Neurologic

17

20

12

Allergic

22

28

1
3

3
3

Hepatobiliary

Constitutional

19

37

Hematologic

74

102

Other
Total

3
30

149
486

5
17

0
4

5
71

162
608

Elicited

Spontaneous

Unknown

Total

Open

65

80

Double blind

Single blind
Case reports

2
0

0
0

Pharmacokinetic

Unknown

Total

20

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12 articles. A large proportion of these deaths (n 5 33, 54.1%)

were identified in 1 article and were insufficiently characterized
to assess drug exposure or attribution of drug and outcome [23].
Variable amounts of detail were available for the remaining cases
(n 5 28, 45.9%), and after full review, none provided sufficient
data to demonstrate causal attribution to FA [2433].
In addition to death, hepatic AEs require specific consideration. As drugs marketed in the European Union have often
elicited hepatotoxicity safety signals that have precluded their
approval in the United States (eg, ibufenac, perhexiline, alpidem), specific attention was placed on hepatic abnormalities
during the literature survey. Two patients had documented
concomitant elevation of hepatic enzymes and bilirubin,
a combination that warrants further review. One patient was
receiving concomitant protease inhibitorbased highly active
antiretroviral therapy and was found to have supratherapeutic
levels of FA, saquinavir, and ritonavir, most likely due to cytochrome P450 CYP3A4 inhibition by the protease inhibitors. The
elevations in bilirubin and hepatic enzyme levels could not
conclusively be attributed to FA exposure due to concomitant
exposure with a known potentially hepatotoxic agent [34]. The
second case was confounded due to AIDS co-morbidity and
concomitant use of potentially hepatotoxic agents (sulfadoxine
and pyrimethamine, Fansidar) as well as a CYP3A4 inhibitor
(ketoconazole). In this case, elevations in bilirubin and hepatic
enzyme levels may have been attributable to disease state and/or
use of a known hepatotoxic drug [31].
In the interest of summarizing the surveyed literature with
regard to character and frequency of adverse events, focus was
placed on the most salient experience in the published literature,
which is in skin infections (20 citations) and osteomyelitis (19
citations). When the assessment of FA-treated subjects was
limited to those who had received treatment for skin infections
in comparative studies, 2066 total subjects were identified, of
whom 876 were treated with FA and 1190 were treated with
a comparator. The overall character of AEs was similar among
these pooled groups with a prevalence of gastrointestinal, neurologic, and allergic events. This AE profile was comparable to
the 608 total AEs captured for all skin infection subjects treated

Table 5. Terms Used to Identify Skin Infections in the VigiBase

Database Extract
Cellulitis and abscess of finger and toe
Cellulitis and abscess of toe
Cellulitis and abscess of unspecified digit
Cellulitis and abscess, other
Cellulitis of finger
Chronic ulcer of skin
Contact dermatitis and other eczema
Contact dermatitis and other eczema, unspecified cause
Cutaneous abscess, furuncle and carbuncle
Erysipelas
Folliculitis decalvans
Impetigo
Local infections of skin and subcutaneous tissue
Local infections of skin and subcutaneous tissue, other
Open wound(s) of unspecific site without mention of complication
Open foot wound, not toe alone
Other infection of skin and subcutaneous tissue
Other cellulitis and abscess
Other cellulitis and abscess, multiple and unspecified cause
Other eczema and dermatitis, other and unspecified cause
Other, multiple and unspecified open wounds, head, neck, and trunk
Postoperative infection
Postoperative wound infection
Staphylococcal infection, unspecified
Streptococcal infection, unspecified
Staphylococcus, bacterial infection
Streptococcus, bacterial infection
Superficial injury of trunk
Ulcer of lower limb, not elsewhere classified
Ulcer of lower limbs, except decubitus
Unspecified local infection of skin and subcutaneous tissue

The majority of cases detailed in the VigiBase data extract

were in the adult and geriatric populations (88.0%), with no
significant difference in gender (48.1% female and 50.5%
male); neonate and pediatric cases constituted a smaller proportion of the cases (.4% and 5.8%, respectively), and 5.9% of
cases were not specifically categorized. There were a total of
1476 events among these 824 subjects, with the largest number
of reports originating from Sweden, France, Great Britain, and
Australia. Events occurred most frequently in the following
categories: hepatobiliary, allergic, hematologic, gastrointestinal, and neurologic, which is in agreement with current
product labeling and safety data identified from the published
literature. There were 50 patients identified as having been
treated for a skin infection (as defined by one of the terms in
Table 5) in the VigiBase data extract, who were dosed, on
average, 500 mg 3 times daily. Treatment duration was captured in the AE report for 40 of these subjects; the majority
(n 5 35, 85%) received <14 days of therapy. For the 18 subjects who were treated for osteomyelitis, 12 had treatment
duration as a captured variable, of which the majority (n 5 8,
67%) received <14 days of FA therapy.
A total of 83 of the AEs (5.6% of the 1476 events) were directly
associated with skin infections of which the majority were categorized as allergic or hepatobiliary. A total of 34 events (2.3% of
all events) were associated with treatment for osteomyelitis.
There were no events that exceeded 10 in number per system
category for osteomyelitis, but hepatobiliary and gastrointestinal
events remained prominent (Table 6). There were no associated
deaths in this group, which is notable since the average treatment duration for osteomyelitis is substantially longer than for
skin infections as was evident in both the VigiBase extract and
the published literature. There was no indication of greater
toxicity at higher dose or duration regimens.
Thirty-nine deaths were reported from 23 countries between
1968 and 2007 with the highest proportion from the United
Kingdom (43.6%) and France (25.6%). The majority of these
deaths were in the geriatric and adult age groups (61.5% and
30.8%, respectively), as well as 1 pediatric death and 2 deaths for
which the demographic details were not available. Most of these
deaths were deemed to be either unrelated to FA or the detail of
relatedness was not provided (30% and 37.5%, respectively),
with 33% (n 5 13) listed as related to FA. Among the 13 deaths
listed as potentially related to FA exposure, 11 were classified
under the hepatobiliary system and where the data field was
available (n 5 8), the reports originated from a hospital setting
or from a specialist physician (Table 7). It is not clear from the
data extract whether the primary cause for hospitalization was
related to the AE or if the AE occurred during the care of the
patient for another reason. Almost no reports listed a treatment
indication (n 5 38, 97%); there was only 1 that identified a skin
infection. This patient was an 85-year-old hospitalized Swedish
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VigiBase is a centralized database of spontaneous safety reports that is managed by the Uppsala Monitoring Centre
(UMC) and under the remit of the World Health Organization
(WHO). It is fully compliant with the Medical Dictionary for
Regulatory Activities (MedDRA) and employs both the WHO
Adverse Drug Reaction Terminology (WHOART) and WHO
Drug dictionaries. As of April 2007, VigiBase comprised more
than 3.8 million case reports submitted from 84 countries, with
approximately 50,000 cases reported quarterly. Full data extracts
of all adverse event reports for FA received and processed at the
UMC were requested with categorization by route of administration to cover intravenous, topical, and oral administration. A
total of 824 unique patients were identified in the VigiBase data
extract. These 824 patients had a primary reference of an AE
linked to the oral formulation of FA, and the data extract was
limited to unique records (duplicates were excluded) as well as
the most recent updated report (updated reports for the same
event were removed).

Table 6. Adverse Events Identified in VigiBase Data ExtractFusidic Acid (as of April 2007)
Osteomyelitis Skin infection Not stated Total
Gastrointestinal

11

162

179

Constitutional

74

78

Nervous

51

54

Allergic

28

263

298

Hepatobiliary

18

392

414

Hematologic

193

206

Respiratory

16

18

Other
Cardiovascular

2
0

3
2

46
21

51
23

Renal

36

39

Musculoskeletal

29

35
24

Dermatologic

23

Psychiatric

13

15

Infectious

11

11

0
0

1
0

4
19

5
19

Total

34

83

1359

1476

woman with a postoperative wound infection who subsequently

developed hepatorenal syndrome. There were no reported
deaths for which the indication of osteomyelitis was listed.
DISCUSSION
This review has assessed the reporting of FA adverse events as
detailed in available product labels, the published literature, and
the spontaneous reporting system in non-US markets as a means
of qualitatively characterizing the safety profile of oral FA with
a targeted focus on skin infection treatment. Applying this

Table 7. Preferred Terms for Deaths in VigiBase Data Extract Associated With Fusidic Acid Exposure
Hospital

Not stated

Specialist physician

Other

Total

Died

14

Body as a wholegeneral disorders

Liver and biliary system disorders

3
1

Musculoskeletal system disorders

Vascular (extracardiac) disorders
Diedreaction may be contributory

1
7

Central and peripheral nervous system disorders

Gastrointestinal system disorders

Liver and biliary system disorders

1
1
5

Diedunrelated to reaction

Liver and biliary system disorders

20

1
13

1
5

Respiratory system disorders

White cell and RES disorders
Total
NOTE.

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RES, reticuloendothelial system.

CID 2011:52 (Suppl 7)

Kraus and Burnstead

1
13

11
1

12
10

1
39

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Inflammatory
Not stated
Endocrine/metabolic

approach to evaluating FA safety entailed accessing information

located on regulatory agencies safety databases, the UMC database, and the available published literature. Since only 1 oral
agent in the United States, linezolid, has an FDA-approved indication for treatment of MRSA infections, all other oral agents
are currently being used off-label. Characterizing the available
safety data sources can provide clinicians a useful perspective of
potential safety concerns experienced by non-US colleagues for
this oral anti-staphylococcal agent should it eventually gain
marketing approval in the US.
Based on the available data from the published literature, as
well as spontaneous reports, exposure to oral FA over the previous 4 decades has been significant and clearly greatest for skin
infection indications. Fusidic acid, when used orally 500 mg 2 or
3 times daily for 7 to 14 days to treat patients with skin infections, demonstrates safety characteristics consistent with the
non-US product labeling, based on spontaneous reports as well
as the surveyed literature. Serious events such as death and
hospitalization were identified for FA-exposed patients in both
the published literature as well as non-US spontaneous reports,
but there were no clinically convincing cases demonstrating
attribution of the adverse event to FA exposure alone. Similarly,
hepatotoxic events identified in the literature were either confounded as to attribution, were lacking significant clinical information to allow critical clinical assessment, or were deemed
to be potentially related, but not of significant concern, by the
respective authors. Specific signals identified related to hyperbilirubinemia are unlikely due to direct toxicity, but rather are
a consequence of bile transporter inhibition, similar to DubinJohnson syndrome [37]. Although reports on FA safety have
continued since this safety data evaluation was conducted at
the close of 2007, such reports remain consistent with current
non-US product labeling and reflect the safety characteristics

described in this review, including FA and statin interactions

[3840]. By having a better understanding of known risk characteristics, appropriate patient selection can be enhanced. Conclusions regarding overall safety must also be tempered by the
data quality associated with this survey. The available literature
comprised mostly open-label studies and disparate safety data
collection methodologies. Few controlled studies were available
and fewer yet that employed randomization or the use of a placebo. For this reason, actual rates were not explicitly provided for
AEs. Regretfully, the surveyed data were inconsistent across
studies, often lacked critical information regarding potential
confounders, and rarely provided the methodology of safety data
collection. Given the aforementioned lack of consistency across
studies with absent methodologies in many of the citations, we
consider the survey as providing signals that require attention in
Appendix.

the design and conduct of adequate and well-controlled clinical

studies of FA for potential registration in the United States. Access to foreign market experience is vital to maximize the data
captured in future randomized controlled trials and the need
remains to characterize identified safety concerns, both as monotherapy and in combination treatment regimens, where other
medications may be co-administered (eg, rifamipicin).
Acknowledgments
Supplement sponsorship. This article was published as part of a supplement entitled "Fusidic Acid Enters the United States" sponsored by
Cempra Pharmaceuticals.
Potential conflicts of interest. C. N. K. has served as a consultant for
Nanotherapeutics, Cempra Pharmaceuticals, bioMerieux, GeneProbe,
BioAlliance Pharma, and Alnylam Pharmaceuticals. B. W. B. has served as
a consultant for CDISC and Comac Medical.

Reviewed Literature Citations

Year

Citation

1962

R. Penman. Fusidic acid in bacterial endocarditis. Lancet 280(7268):12771278, 1962. (ScienceDirect)

1962

E.F. Scowen and L.P. Garrod. A case of staphylococcal septicaemia treated with penicillin and
fucidin. Lancet 279 (7236):933935. 1962. (ScienceDirect)

1962

E.J. Lowbury, D.M. Jackson, J.S. Cason, and R.W.S. Miller. Fucidin for Staphylococcal infection
in burns. Lancet 280 (7254):478480, 1962.

1963

I.A. Porter and J.S.P. Wilson. Staphylococcal infections treated with fusidic acid in nurses. Lancet
282 (7309):658659, 1963.

1963

E.H. Chater. Clinical trial of fucidin in bone and joint infections. Ir J Med Sci 6th series:367373,
1963.

1963

R.B. Crosbie. Treatment of Staphylococcal infections with "fucidin." Br Med J 1 (5333):788794,

1963.

1965

V. Wynn. Metabolic effects of the steroid antibiotic fusidic acid. Br Med J 1 (5477):14001404,
1965.

1966

R.D. Thornes and M.V. Sheehan. Fucidin therapy in carcinoma of the breast. (Preliminary
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